Mutagenetix > Incidental Mutation

Incidental Mutation 'R1654:Nlrp3'

188956

Institutional Source

Beutler Lab

Gene Symbol

Nlrp3

Ensembl Gene

ENSMUSG00000032691

Gene Name

NLR family, pyrin domain containing 3

Synonyms

Cias1, cryopyrin, Pypaf1, NALP3, Mmig1

MMRRC Submission

039690-MU

Accession Numbers

Ncbi RefSeq: NM_145827.3; MGI:2653833

Essential gene?

Probably non essential (E-score: 0.081) question?

Stock #

R1654 (G1)

Quality Score

225

Status

Not validated

Chromosome

Chromosomal Location

59541568-59566956 bp(+) (GRCm38)

Type of Mutation

missense

DNA Base Change (assembly)

T to C at 59543123 bp (GRCm38)

Zygosity

Heterozygous

Amino Acid Change

Valine to Alanine at position 4 (V4A)

Ref Sequence

ENSEMBL: ENSMUSP00000114231 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000079476] [ENSMUST00000101148] [ENSMUST00000149126]

AlphaFold

Q8R4B8

Predicted Effect

probably benign
Transcript: ENSMUST00000079476
AA Change: V4A

PolyPhen 2 Score 0.003 (Sensitivity: 0.98; Specificity: 0.44)

SMART Domains

Protein: ENSMUSP00000078440
Gene: ENSMUSG00000032691
AA Change: V4A

Domain	Start	End	E-Value	Type
PYRIN	4	87	6.39e-33	SMART
FISNA	135	206	1.45e-22	SMART
Pfam:NACHT	216	385	6.7e-52	PFAM
low complexity region	533	539	N/A	INTRINSIC
low complexity region	688	697	N/A	INTRINSIC
LRR_RI	737	764	1.07e-9	SMART
LRR	766	793	5.13e1	SMART
LRR	794	821	3.86e-7	SMART
LRR	823	850	1.62e0	SMART
LRR	851	878	3.39e-3	SMART
LRR	880	907	1.2e2	SMART
LRR	908	935	2.24e-3	SMART
LRR	937	964	2.16e2	SMART
LRR	965	992	8.73e-6	SMART

Predicted Effect

probably benign
Transcript: ENSMUST00000101148
AA Change: V4A

PolyPhen 2 Score 0.003 (Sensitivity: 0.98; Specificity: 0.44)

SMART Domains

Protein: ENSMUSP00000098707
Gene: ENSMUSG00000032691
AA Change: V4A

Domain	Start	End	E-Value	Type
PYRIN	4	87	6.39e-33	SMART
FISNA	135	206	1.45e-22	SMART
Pfam:NACHT	216	385	6.7e-52	PFAM
low complexity region	533	539	N/A	INTRINSIC
low complexity region	688	697	N/A	INTRINSIC
LRR_RI	737	764	1.07e-9	SMART
LRR	766	793	5.13e1	SMART
LRR	794	821	3.86e-7	SMART
LRR	823	850	1.62e0	SMART
LRR	851	878	3.39e-3	SMART
LRR	880	907	1.2e2	SMART
LRR	908	935	2.24e-3	SMART
LRR	937	964	2.16e2	SMART
LRR	965	992	8.73e-6	SMART

Predicted Effect

probably benign
Transcript: ENSMUST00000149126
AA Change: V4A

PolyPhen 2 Score 0.030 (Sensitivity: 0.95; Specificity: 0.82)

SMART Domains

Protein: ENSMUSP00000114231
Gene: ENSMUSG00000032691
AA Change: V4A

Domain	Start	End	E-Value	Type
PYRIN	4	87	6.39e-33	SMART
Pfam:FISNA	135	173	1.6e-12	PFAM

Coding Region Coverage

1x: 99.1%
3x: 98.4%
10x: 96.5%
20x: 93.0%

Validation Efficiency

MGI Phenotype

Strain: 3686871
FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] This gene encodes a pyrin-like protein containing a pyrin domain, a nucleotide-binding site (NBS) domain, and a leucine-rich repeat (LRR) motif. This protein interacts with the apoptosis-associated speck-like protein PYCARD/ASC, which contains a caspase recruitment domain, and is a member of the NALP3 inflammasome complex. This complex functions as an upstream activator of NF-kappaB signaling, and it plays a role in the regulation of inflammation, the immune response, and apoptosis. Mutations in this gene are associated with familial cold autoinflammatory syndrome (FCAS), Muckle-Wells syndrome (MWS), chronic infantile neurological cutaneous and articular (CINCA) syndrome, and neonatal-onset multisystem inflammatory disease (NOMID). Multiple alternatively spliced transcript variants encoding distinct isoforms have been identified for this gene. Alternative 5' UTR structures are suggested by available data; however, insufficient evidence is available to determine if all of the represented 5' UTR splice patterns are biologically valid. [provided by RefSeq, Oct 2008]
PHENOTYPE: Mice homozygous for null mutations exhibit attenuated inflammatory responses related to decrease secretion of IL-1beta and IL-18. Mice heterozygous for activating mutations suffer from autoinflammatory attacks that lead to organ failure and death before weaning. [provided by MGI curators]

Allele List at MGI

All alleles(13) : Targeted(9) Chemically induced(4)

Other mutations in this stock

Total: 77 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
1700012B07Rik	C	T	11: 109,797,399	S90N	probably benign	Het
Apc2	C	T	10: 80,301,842	T39I	possibly damaging	Het
Arfgef3	C	T	10: 18,625,148	R1118K	probably null	Het
Arhgef12	T	C	9: 42,997,660	D658G	possibly damaging	Het
Asph	G	T	4: 9,453,315	R736S	probably benign	Het
Bcas1	C	T	2: 170,349,246	G542E	probably damaging	Het
Brd8	A	T	18: 34,611,226	V183E	probably damaging	Het
C1rl	G	A	6: 124,493,910	G59E	probably damaging	Het
Cacna1i	C	A	15: 80,389,210	A1699D	probably damaging	Het
Card6	G	T	15: 5,098,732	Q1061K	probably benign	Het
Cd163	G	T	6: 124,317,581	C566F	probably damaging	Het
Cd84	C	T	1: 171,884,606	T263I	possibly damaging	Het
Cep63	T	C	9: 102,586,913	I740V	possibly damaging	Het
Chaf1b	C	A	16: 93,894,903	A279D	probably damaging	Het
Chsy3	A	T	18: 59,176,416	Y247F	probably damaging	Het
Cpxm1	G	A	2: 130,393,546	L509F	possibly damaging	Het
Disc1	A	T	8: 125,148,465	Q558L	possibly damaging	Het
Dnah3	A	T	7: 119,926,449	L3894Q	probably damaging	Het
Dnmt1	G	T	9: 20,936,574	T105N	possibly damaging	Het
Dock6	A	T	9: 21,804,843	L1732Q	probably damaging	Het
Dsc2	T	C	18: 20,046,246	N255S	probably benign	Het
Dsel	A	T	1: 111,862,512	Y98N	probably damaging	Het
Enox1	T	A	14: 77,611,374	I375N	possibly damaging	Het
Epha4	T	A	1: 77,374,768		probably null	Het
Fam71a	T	C	1: 191,163,481	R322G	probably benign	Het
Fktn	A	G	4: 53,761,220	I446V	probably benign	Het
Gm7361	G	T	5: 26,261,099	R153L	probably damaging	Het
Grin2c	C	T	11: 115,260,853	V94I	probably benign	Het
Kalrn	T	G	16: 33,975,738	L1222F	probably damaging	Het
Krt80	T	C	15: 101,351,709	K255E	probably damaging	Het
Lcn6	T	A	2: 25,680,775		probably null	Het
Lonp2	T	G	8: 86,631,450	L100V	probably damaging	Het
Lyn	G	A	4: 3,789,912	A482T	probably damaging	Het
Mapk4	A	G	18: 73,930,939	F404S	probably damaging	Het
Mast2	T	C	4: 116,316,550		probably null	Het
Medag	T	C	5: 149,422,135	Y94H	probably damaging	Het
Megf8	T	C	7: 25,338,486	L809P	possibly damaging	Het
Mgam	T	C	6: 40,757,487	S743P	probably damaging	Het
Mia2	C	A	12: 59,108,833	T445K	possibly damaging	Het
Nars	C	G	18: 64,512,049	A43P	probably damaging	Het
Nav3	T	C	10: 109,853,123	N431S	possibly damaging	Het
Ndufaf5	A	G	2: 140,177,300		probably null	Het
Nlrp1b	T	G	11: 71,181,298	E573A	probably damaging	Het
Olfr1389	G	A	11: 49,430,502	G9R	probably benign	Het
Olfr194	T	C	16: 59,119,689	N127S	possibly damaging	Het
Olfr661	A	T	7: 104,688,213	Y66F	probably benign	Het
Pcdhb12	A	T	18: 37,436,701	D300V	probably damaging	Het
Pik3c2a	A	T	7: 116,368,848	C804S	probably benign	Het
Pkp4	A	T	2: 59,337,619	Q725L	probably damaging	Het
Ptpre	T	A	7: 135,653,928	S119T	probably benign	Het
Ptprk	G	A	10: 28,383,647	R361H	probably damaging	Het
Ptprr	T	C	10: 116,188,363	V193A	probably benign	Het
Rfx2	C	T	17: 56,808,263	A19T	probably benign	Het
Rgs4	T	A	1: 169,745,311	M19L	probably benign	Het
Rnf157	T	C	11: 116,358,715	H225R	probably damaging	Het
Rnf44	A	T	13: 54,681,779	D341E	possibly damaging	Het
Sct	T	A	7: 141,278,854	Q55L	probably damaging	Het
Sh3rf1	A	T	8: 61,361,745	H446L	possibly damaging	Het
Shisa3	A	T	5: 67,611,059	I101F	probably damaging	Het
Slc6a13	A	G	6: 121,336,926	I543V	probably benign	Het
Soga3	A	T	10: 29,146,935		probably null	Het
Spef2	G	A	15: 9,634,652	A1024V	probably damaging	Het
St6galnac6	T	C	2: 32,619,509	S330P	probably damaging	Het
Stard9	G	T	2: 120,703,722	A3487S	probably benign	Het
Suclg2	T	C	6: 95,655,551	S46G	probably damaging	Het
Syne2	T	C	12: 76,101,094	V6469A	possibly damaging	Het
Tada2b	C	T	5: 36,483,795	G88D	probably damaging	Het
Tll1	A	T	8: 64,117,903		probably null	Het
Tph2	T	A	10: 115,184,807	H28L	probably benign	Het
Trmt6	C	A	2: 132,815,835	V34L	possibly damaging	Het
Ttc22	A	G	4: 106,634,211	T204A	probably damaging	Het
Umodl1	A	T	17: 30,987,968	M778L	probably benign	Het
Vcan	T	C	13: 89,661,946	H2282R	probably damaging	Het
Vmn2r77	T	A	7: 86,811,915	S816R	probably damaging	Het
Vps13c	T	A	9: 67,951,687	F2806L	probably damaging	Het
Zbtb4	C	A	11: 69,779,169	A906D	probably damaging	Het
Zscan29	A	G	2: 121,164,779	V421A	probably benign	Het

Other mutations in Nlrp3

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL00421:Nlrp3	APN	11	59565943	missense	probably damaging	0.99
IGL00573:Nlrp3	APN	11	59565116	missense	possibly damaging	0.93
IGL01025:Nlrp3	APN	11	59551887	missense	probably benign	0.21
IGL01637:Nlrp3	APN	11	59549378	missense	probably damaging	0.99
IGL02010:Nlrp3	APN	11	59549535	missense	probably benign
IGL02334:Nlrp3	APN	11	59565083	missense	probably benign
IGL02417:Nlrp3	APN	11	59566023	unclassified	probably benign
IGL02578:Nlrp3	APN	11	59548401	missense	probably damaging	1.00
IGL02710:Nlrp3	APN	11	59565976	missense	probably damaging	0.99
IGL02816:Nlrp3	APN	11	59555782	missense	probably benign	0.03
IGL03157:Nlrp3	APN	11	59549546	missense	possibly damaging	0.80
IGL03334:Nlrp3	APN	11	59549016	missense	probably damaging	1.00
Flogiston	UTSW	11	59558448	missense	probably benign	0.00
nd1	UTSW	11	59565974	missense	probably benign	0.45
Nd14	UTSW	11	59555875	missense	possibly damaging	0.89
Nd3	UTSW	11	59565974	missense	probably benign	0.45
nd5	UTSW	11	59565879	missense	probably benign	0.01
nd6	UTSW	11	59549354	missense	probably damaging	1.00
nd7	UTSW	11	59555875	missense	possibly damaging	0.89
Nd9	UTSW	11	59549354	missense	probably damaging	1.00
Park2	UTSW	11	59565128	nonsense	probably null
Park3	UTSW	11	59565850	missense	probably benign	0.02
Park4	UTSW	11	59549531	missense	probably benign	0.19
Park5	UTSW	11	59548476	missense	probably damaging	0.99
Park6	UTSW	11	59549036	missense	probably damaging	1.00
Park7	UTSW	11	59548010	nonsense	probably null
Park8	UTSW	11	59566199	missense	probably benign	0.19
R0008:Nlrp3	UTSW	11	59558448	missense	probably benign	0.00
R0008:Nlrp3	UTSW	11	59558448	missense	probably benign	0.00
R0052:Nlrp3	UTSW	11	59565128	nonsense	probably null
R0362:Nlrp3	UTSW	11	59548797	missense	possibly damaging	0.49
R0416:Nlrp3	UTSW	11	59555924	splice site	probably benign
R0649:Nlrp3	UTSW	11	59548542	missense	possibly damaging	0.83
R0740:Nlrp3	UTSW	11	59548256	missense	probably benign	0.01
R0863:Nlrp3	UTSW	11	59565850	missense	probably benign	0.02
R1300:Nlrp3	UTSW	11	59555768	missense	possibly damaging	0.86
R1414:Nlrp3	UTSW	11	59549531	missense	probably benign	0.19
R1622:Nlrp3	UTSW	11	59548476	missense	probably damaging	0.99
R1715:Nlrp3	UTSW	11	59543351	missense	probably damaging	1.00
R1754:Nlrp3	UTSW	11	59558402	missense	possibly damaging	0.80
R1837:Nlrp3	UTSW	11	59548916	missense	probably benign	0.00
R1905:Nlrp3	UTSW	11	59549036	missense	probably damaging	1.00
R2281:Nlrp3	UTSW	11	59549136	missense	possibly damaging	0.70
R4296:Nlrp3	UTSW	11	59549661	missense	possibly damaging	0.89
R4305:Nlrp3	UTSW	11	59548010	nonsense	probably null
R4540:Nlrp3	UTSW	11	59551899	missense	possibly damaging	0.83
R4591:Nlrp3	UTSW	11	59549222	missense	probably benign	0.00
R4816:Nlrp3	UTSW	11	59548301	missense	probably benign	0.32
R4913:Nlrp3	UTSW	11	59549238	missense	probably benign	0.09
R4970:Nlrp3	UTSW	11	59548728	missense	probably damaging	1.00
R5051:Nlrp3	UTSW	11	59566199	missense	probably benign	0.19
R5112:Nlrp3	UTSW	11	59548728	missense	probably damaging	1.00
R5185:Nlrp3	UTSW	11	59565084	missense	probably benign	0.05
R5417:Nlrp3	UTSW	11	59549063	missense	probably damaging	1.00
R5709:Nlrp3	UTSW	11	59555748	nonsense	probably null
R5869:Nlrp3	UTSW	11	59548134	missense	probably damaging	1.00
R5898:Nlrp3	UTSW	11	59546852	missense	probably benign	0.00
R5953:Nlrp3	UTSW	11	59546791	missense	probably benign
R5979:Nlrp3	UTSW	11	59548971	missense	probably benign	0.06
R6359:Nlrp3	UTSW	11	59548566	missense	probably damaging	0.97
R6723:Nlrp3	UTSW	11	59565192	missense	probably damaging	1.00
R7261:Nlrp3	UTSW	11	59548446	missense	possibly damaging	0.83
R7349:Nlrp3	UTSW	11	59548086	missense	probably damaging	1.00
R7388:Nlrp3	UTSW	11	59565066	missense	probably benign	0.00
R7715:Nlrp3	UTSW	11	59543003	splice site	probably null
R7916:Nlrp3	UTSW	11	59551863	missense	probably benign	0.00
R8222:Nlrp3	UTSW	11	59548788	missense	probably damaging	0.98
R8360:Nlrp3	UTSW	11	59549403	missense	probably benign	0.02
R8390:Nlrp3	UTSW	11	59551790	missense	possibly damaging	0.47
R8550:Nlrp3	UTSW	11	59549271	missense	probably damaging	1.00
R8738:Nlrp3	UTSW	11	59549390	missense	probably benign	0.00
R8940:Nlrp3	UTSW	11	59565044	missense	probably benign	0.26
R8990:Nlrp3	UTSW	11	59548758	missense	probably damaging	0.99
R9324:Nlrp3	UTSW	11	59543315	missense	probably damaging	1.00
R9673:Nlrp3	UTSW	11	59549322	missense	probably damaging	1.00
RF031:Nlrp3	UTSW	11	59558552	frame shift	probably null
RF040:Nlrp3	UTSW	11	59558552	frame shift	probably null
Z1088:Nlrp3	UTSW	11	59551860	missense	possibly damaging	0.67

Predicted Primers

PCR Primer
(F):5'- CTCAGGACATACGTCTGGATCAAGC -3'
(R):5'- TCGCCTGTTGATCGCAGCAAAG -3'

Sequencing Primer
(F):5'- AAACCTGTACCAATCTATGGGG -3'
(R):5'- GTTGATCGCAGCAAAGATCCAC -3'

Posted On

2014-05-09